PROJECT SUMMARY/ABSTRACT Paradoxical vocal fold motion disorder (PVFMD) involves debilitating episodes of abnormal vocal fold closure during respiration and is frequently accompanied with chronic cough. This disorder results in vocal fold tissue irregularities, abnormal voice quality, and impaired voice- and health-related quality of life. The larynx is fundamental in protecting the lower airway against sensory irritants via vocal fold closure. Despite this normal function, odors and sensory irritants are significant triggers of PVFMD. The most recent strategic plan of the National Institute on Deafness and Other Communication Disorders has acknowledged that vocal fold function, co-occurring factors that contribute to vocal fold disorders, and translational research in the chemical senses of smell (olfaction) and sensory irritation (chemesthesis) are high-priority areas of research. Critical barriers to progress in understanding PVFMD are the lack of standardization of odor and irritant stimuli to elicit symptoms, limited outcome measures for assessing sensory irritation of the upper airway, and poor objective measures of chronic cough. These limitations significantly reduce the accuracy of diagnosis and treatment monitoring, and greatly impact the study of the pathogenesis underlying odor- and irritant-induced PVFMD. Preliminary studies demonstrated that sensory irritation of the upper airway is measurable during exposure to a chemosensory stimulus. These findings led to the central hypothesis of this proposal: both perceptual and physiological responses to odors and sensory irritants occur in the normal laryngeal system. The goal of the proposed research is to develop measures that assess the contribution of odors and sensory irritants on normal and abnormal laryngeal responses. The specific aims of the proposal are (1) to quantify changes in upper airway sensory irritation before, during, and after exposure to an odor and sensory irritant using labeled magnitude scaling procedures, and (2) to quantify changes in vocal fold compression phase duration during exposure to high versus low concentrations of sensory irritants using aerodynamic cough analysis. These aims will be addressed using improved methods to systematically prepare and deliver controlled odor and irritant stimuli, principles of human psychophysics to measure perceptual changes in sensation of the upper airway, and aerodynamics analyses to measure physiological changes in cough airflow. Findings from Aim 1 will provide a necessary foundation for understanding how the chemical senses mediate normal sensations of upper airway irritation in healthy participants, leading to the development of improved psychophysical scales as outcome measures to differentially diagnose PVFMD. Completion of Aim 2 will elucidate how a variety of sensory irritants influence aerodynamic measures of cough, leading to future standardization of objective testing to elicit symptoms related to vocal fold closure. Taken together, the proposed research will lead to necessary research efforts implementing non-invasive testing to diagnose and characterize the severity of PVFMD.